PROJECT SUMMARY/ABSTRACT - Vascular Effects of Dietary Salt in Humans with Salt-Resistant BP Cardiovascular disease remains a major Public Health problem and is the leading cause of death in the US. Dietary salt restriction is considered an important lifestyle modification for individuals with hypertension; however, there is controversy about the effects of dietary salt given that many individuals do not have ?salt sensitive? BP. Indeed, the vast majority of normotensive adults have salt resistant BP. Yet, we have recently shown that excess dietary salt loading causes a reduction in conduit artery function and microvascular function, independent of changes in BP. Reduced nitric oxide (NO) bioavailability linked to increased oxidative stress is one of the contributing mechanisms, however the source of reactive oxygen species (ROS) has yet to be elucidated. Further, a high salt intake has been shown to increase wave reflection from the periphery and left ventricular (LV) afterload. Alterations in the endothelium likely contribute to this by altering the pulsatile arterial load on the heart. Based on the foregoing, our global hypothesis is that dietary salt restriction will lower oxidative stress, improve endothelial function, and improve central arterial pulsatile hemodynamics. We propose to investigate the effects of dietary salt restriction on vascular function and the pulsatile load on the LV in men and women. Specifically, we hypothesize that dietary salt restriction will improve central hemodynamics, arterial stiffness, endothelial?dependent dilation and NO-mediated cutaneous vasodilation. We also hypothesize that oxidative stress will decrease during dietary salt restriction, and that NADPH oxidase is the source of these ROS. Young and middle-aged salt resistant adults will undergo dietary counseling to follow a low sodium diet for 30-days. Ambulatory BP, urine collections, and vascular measures will occur pre- and post-intervention. Reflection magnitude, forward wave amplitude, aortic characteristic impedance and stiffness will be assessed to characterize central hemodynamics. Flow mediated dilation of the brachial artery will be used to assess conduit endothelial?dependent dilation and cutaneous vasodilation in response to local heating using laser Doppler flowmetry and intradermal microdialysis will be assessed to evaluate the microvasculature. Cutaneous vasodilation in response to local heating will be assessed at a Ringers site (control), L-NAME site (NO contribution), an ascorbic acid site (role of oxidative stress), an apocynin site (role of NADPH oxidase) and a tempol site (role of superoxide). Endothelial cells will be also obtained to assess oxidant damage as well as oxidant and antioxidant enzyme content. This comprehensive assessment of central hemodynamics and endothelial function in humans during a dietary sodium restriction intervention will allow us to determine if lowering dietary salt improves central hemodynamics and endothelial-dependent vasodilation and whether sex specific differences exist in response to dietary salt restriction. Findings will be distributed to the scientific community and others through implementation of a comprehensive dissemination plan.